Você está na página 1de 20

10

Ophtalmia Neonatorum
Flora Abazi, Mirlinda Kubati, Blerim Berisha, Masar Gashi,
Dardan Koinaj and Xhevdet Krasniqi
University Clinical Centre of Kosovo
Republic of Kosovo

1. Introduction
Sexually transmitted infections (STIs) or sexually transmitted diseases (STDs) are common in
low- income countries. Among adult women STIs (excluding HIV) represent around 9% of the
disease burden (World Bank, 1993). This group of disease (Table 1) can lead to infertility,
abortion, neonatal blindness and sometimes death. Furthermore in up to 75% of women STIs
are thought to be asymptomatic, knowing also that vaginal discharge might be caused by non-
sexually transmitted changes in vaginal flora (Sloan et al., 2000; Lush et al., 2003).

Common STI syndrome Possible cause

Chancroid, Syphilis, Chlamydia, Herpes


Genital ulcer disease
simplex virus, Donovanosis
Urethral discharge Gonorhoea, Chlamydia
Gonorhoea, Chlamydia, Herpes,
Vaginal discharge
trichomonas, Candida, Bacterial vaginosis
Pelvic inflammatory disease Gonorhoea, Chlamydia
Ophtalmia neonatorum Gonorhoea, Chlamydia
Table 1. Common STI syndromes and possible causes Modified from Lush L, Walt G, Ogden
J. (2003) Transferring policies for treating sexually transmitted infections: whats wrong with
global guidelines? Health Policy and planning 18(1): 18-30.
Ophtalmia neonatorum (neonatal conjunctivitis) is an ocular redness, swelling and drainage
(sometimes even purulent) due to a pathogenic organism or even chemical irritant occurring in
infants less than 4 weeks of age with potentially serious ocular and systemic consequences
(Merck Manual 2006, Rudolphs 2002). The frequency of this disease varies up to 19% and is
related to prenatal care (Rudolphs 2002).
Bacterial infection is acquired from infected mother during delivery. The most common
bacteria is Chlamydia trachomatis causing Chlamydial ophtalmia occurring in 2 to 4% of
births. This entity accounts for about one third to half of all conjunctivitis in neonates,
characterizing developed countries (Current, 2009), while the prevalence of maternal
chlamidial infection ranges from 2 to 20% (Mohile et al., 2002) with the incidence increasing
dramatically through years (Miller, 2006).

www.intechopen.com
148 Conjunctivitis A Complex and Multifaceted Disorder

Streptococcus pneumoniae and Haemophilus influenze as other bacteria responsible


account for another 15% of cases. On the other hand, the incidence of conjunctivitis due to
Neisseria gonorrhoeae (gonorrheal ophtalmia) in the USA is 2 to 3 per 10,000 births.
Usually the isolation of other bacteria than mentioned above (e.g. Staphylococcus aureus)
represents colonization.
Herpetic kerato- conjunctivitis caused by herpes simplex virus types 1 and 2 represents the
major viral infection, while chemical conjunctivitis is generally secondary to the instillation
of ocular drops (e.g. silver nitrate) for prophylaxis purpose.

2. Etiology
Ophtalmia neonatorum may be caused by microorganisms (infectious etiology), or may be
sterile (non infectious etiology) from chemical irritants (Table 2). Sterile or non infection
ophtalmia neonatorum usually is caused by silver nitrate during prophylaxis of this entity.
As far as infectious etiology concerns there are different bacteria and viruses known to cause
this disease. The most commonly isolated bacteria are: Chlamydia trachomatis and Neisseria
gonorrhoeae; but also: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus
viridians, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Serratia
marcescens, Proteus, Enterobacter, and Pseudomonas species. Also, Eikenella corrodens has
been reported as a cause of neonatal conjunctivitis (Chhabra et al., 2008). The most
commonly viral cause is Herpes simplex virus (HSV) associated most often with a
generalized herpes simplex infection.

Etiology Percentage (%) Incubation period Associated problems


Chemical Varies 1 ---
Chlamydia
2-40 5-14 Pneumonia
trachomatis
Neisseria Disseminated
<1 2-7
gonorrhoeae infection
Disseminated
HSV <1 6-14
infection
Table 2. Pathogens of neonatal conjunctivitis
Modified from "Red Book-Report of the Committee on Infectious Diseases, 29th Edition. The
American Academy of Pediatrics.".http://aapredbook.aappublications.org/.

2.1 Silver nitrate solution


Silver nitrate solution is one the most common sterile causes of ophtalmia neonatorum. It
was used for prophylaxis of ocular gonococcal infections as the most effective agent in
prevention of ophtalmia neonatorum by direct inactivating of Gonococi. Crede's method
was a major advance in preventing of ophtalmia neonatorum using 2% drops of Silver
nitrate (Jatla et al., 2009). Later silver nitrate was found to be toxic for conjunctiva, causing
chemical neonatal conjunctivitis, usually lasting 2-4 days. Because of replacement of silver
nitrate with neomycin and chloramphenicol eye drops, and erythromycin ointment the
incidence of chemical neonatal ophtalmia in the most countries have significantly decreased.

www.intechopen.com
Ophtalmia Neonatorum 149

2.2 Chlamydia trachomatis


It was postulated that unknown agent acquired from the genital tract of mother, is a cause of
abacterial ophthalmia neonatorum (Kroner, 1884). Lindner comes to conclusion that
inclusion of blennorrhoea was due to the trachoma agent, and after techniques evolution in
Ophtalmology the first isolation was performed by Tang et al. This was realized by using
the yolk sac of embryonated eggs and latter followed by isolating chlamydia from the
babyes eyes with inclusion of blennorrhoea, and also from cervix of mother (Linder, 1909;
T'ang et al., 1957; Jones et al., 1959).
Chlamydia trachomatis is an intracellular parasite, one of the common causes of
ophtalmia neonatorum 2-4% of births. Chlamydia trachomatis, based on immunogenic
epitope analysis of the major outer membrane protein (MOMP), differentiates in 18
serovars. D to K serovars are common urogenital and ocular pathogens. Genotype
classification correlates with the serovar classification previously mentioned (Rodriguez
et al., 1993). Even though this classification is practical and accepted among researchers, it
is found increased frequency of C. trachomatis genotype E in neonatal conjunctivitis
(Luca et al., 2010).
It is thought that infants may acquire infection from their immediate surroundings, not only
from mother birth canals. The high incidence of caesarean sections with high incidence of
early onset conjunctivitis suggests in a possibility of intrauterine Chlamydial infection due
to rupture of membrane. These kind of infections with Chlamydia trachomatis are sexually
transmitted and WHO estimated 90 million new cases in 1999 (World Health Organisation,
2010). The developing risk of the Chlamydial infection as a conjunctivitis or pneumonia at
birth is increased with an incidence up to 15% (Schachter et al., 1986; Numazaki et al., 2003;
Rosenman et al., 2003).
In some newborns with Chlamydia conjunctivitis, the infection persists too long with panus
and scarring formation and after this, if this infection is left untreated it may be complicated
even with pneumonia. Prevalence of this conjunctivitis is 8%. (Hobson, 1977; Valencia et al.,
2000; Olatunji, 2004).
Chlamydial conjunctivitis occurs after three days of life but may occur up to two weeks of
life with mucopurulent and less inflamed discharge. Chlamydial conjunctivitis is associated
with low risk of blindness compare to Gonorrheal conjunctivitis.

2.3 Neisseria gonorrhoeae


Neisseria gonorrhoeae was identified by Albert Neisser in 1879 in stained smears of
exudates. Availability of Sulfonamides and Penicillin in 1943 was effective in treating of
Gonorroheae (Kampmeier, 1978; Morton, 1977).
In the past N. Gonorroheae was a common cause of conjuctivitis, but after 1881 based on
observations of Crede (using the silver nitrate) the prevalence as a causative agent of
ophtalmia is decreased, in the industrial zones from 10 to 0.3% (Di Bartolomeo et al.,
2001).
Neisseria species are aerobic, gram negative, non motile and non spore forming. Gonococci
occurs in pairs as diplococcal and have outer membrane overlying, a thin peptidoglycan and
cytoplasmic membrane. The species lacks a true polysaccharide capsule but produces a
surface polyphosphate that provides a hydrophilic, negatively charged surface. The
microbes frequently are seen within phagocytes in Gram stains of clinical specimens
(Noegel et al., 1983).

www.intechopen.com
150 Conjunctivitis A Complex and Multifaceted Disorder

Gonococci have ability to adhere to mucosal epithelial cells and thus can survive, activating
nuclear factor kappa B and activator protein 1, with release of numerous of cytokines and
chemokines (Nauman et al., 1997; Ramsey et al., 1995).
The individual gonococci can invade, replicate intracellulary, and by exocytosis can exit into
the submucosal space (Alexey et al., 2000; Nauman et al., 1999). This lead in a chemotactic
influx of neutrophils resulting in formation of micorabscesses and exudation of purulent
material into lumen of infected tissues. Infection can persist for weeks to months if
untreated because of escape immune response (Gergg et al., 1983; Casey et al., 1986; Shafer
et al., 1986; Kallstrom et al., 1997).
Incubation period of Neisseria gonorrhoeae in eye infection is 2 to 5 days and in some
cases may arise 2 to 3 weeks (Gutman, 2001). Gonococcal conjunctivitis begins as benign
and bilateral with eyelid edema, followed by chemosis. The discharge in the beginning is
sero-sanguineous, later becomes thick and purulent, and may contain also blood. The
infection can spread if treatment is delayed causing complications such as corneal
ulceration and perforation, iridocyclitis, and panophtalmitis. From conjunctiva
gonococcus can spread to cause gonococcus septicemia, arthritis, and other manifestations
(Friendly, 1969).
Staphylococcus aureus can cause ophtalmia neonatorum with purulent discharge. The
treatment consists in topical or systemic antibiotic. In some cases spontaneous resolution can
occur. Also, in Ophtalmia neonatorum are verified methicillin and erythromycin resistant S.
aureus, but serious ophtalmologic infection was not found. In case of erythromycin-resistant
Staphylococcus aureus conjunctivitis is used erythromycin ointment to prevent ophtalmia
neonatorum (Cimolai, 2006; Hedberg et al., 1990).
The group B Streptococcus also may causes ophtalmia neonatorum, and is resolved after 7
days of treatment (Pschl et al., 2002).
Eikenella corrodens is a gram-negative bacillus, fastidious, slow growing, and facultative
anaerobic bacterium. It is found as the normal flora of the human mouth, nasopharynx,
gut, and genitourinary tract. In the last two decades has been recognized as cause of head
and neck infections. It is presented as a cause of neonatal conjunctivitis (Chhabra et al.,
2008).
Neonatal conjunctivitis also is caused from other bacteria such as: Staphylococcus
epidermidis, Streptococcus pneumoniae, Haemophilus species, Klebsiella pneumoniae,
Pseudomonas aeruginosa, and Escherichia coli (Martinez et al., 1993; Olatunji et al., 2007).

2.4 Herpes simplex virus


Herpes simplex virus (HSV) can lead to neonatal keratoconjuctivitis passing to the baby
during childbirth. Although it is rare it might be associated with a generalized herpes
simplex infection (Overall, 1994).

2.5 Risk factors of neonatal conjuctivitis

Risk factors of neonatal conjunctivitis may include:

Maternal infections

Exposure of the infant to infectious organisms

Increased birth weight

Inadequacy of ocular prophylaxis immediately after birth (Gichuhi et al., 2009)


Premature Rupture Of Membranes (Wu et al., 2009)

www.intechopen.com
Ophtalmia Neonatorum 151

Ocular trauma during delivery

Mechanical ventilation

Prematurity

Poor prenatal care

Poor hygienic delivery conditions


Post-delivery infection due to direct contact with health care workers or by

environment
Silver nitrate exposure

3. Clinical findings
The Clinical presentation of Neonatal Conjuctivitis varies depending upon the severity and
the type of infection. The signs and symptoms of ophthalmia neonatorum are similar for
most of the infectious agents (Foster, 1995). Diffuse unilateral or bilateral redness due to
injection of conjuctival vessels is the hallmark. Other common findings incude conjuctival
oedema and discharge. More serious finding include keratitis and orbital celulitis, but also
serious systemic involvement if left untreated (Woods, 2005; Zar, 2005). It is necessary to
make accurate diagnosis in order to begin appropriate treatment which can help to reduce
complications (Table 3).

3.1 Chemical conjunctivitis


It is present with mild injection of conjunctiva with minimal discharge. It is important that
these occur within few hours after application of irritant. Sometimes the persistent redness
of the eye might be folowed by purulent discharge and in that case there is a need for
further laboratory investigation.

3.2 Bacterial conjunctivitis


The occurrence time and severity of clinical features depend on the type of microorganism.
Gonococal conjunctivitis
During this infection there is a severe redness, swelling of conjunctiva and eyeleads, and a
lot of purulent drainage presenting few days after birth (Woods 2005), but may occur later
as hyperacute conjunctival injection and chemosis, lid oedema and severe purulent
discharge. Corneal ulceration and perforation may be associated features (Jackson, 2008).
Hyperacute conjunctivitis has the incubation period 1-7 days (Isenberg et al., 1996; Chandler
et al., 1990), often bilateral and signs are more severe. Serosanguinous exudate may be
replaced by mucopurulent discharge, with development of membranes. A disseminated
gonococcal infection with arthritis, meningitis, pneumonia and sepsis that may lead to death
of an infant is very rare.
Chlamydial conjunctivitis
Cervical infection with Chlamydia carries a risk to the neonate of 18-50% (Vaz et al., 1999;
Schachter et al., 1986; Hollier et al., 2009; Roberts, 2009). The clinical features present at 5 to
14 days after birth with gradually worsening. Eyelids and conjunctiva are redness and
swollen (Figure 1), and mucopurrulent drainage is present. It may also occur severe
swelling and discharge with a course of 6 to 12 weeks (if left untreated) leading to scars of

www.intechopen.com
152 Conjunctivitis A Complex and Multifaceted Disorder

conjunctiva and cornea. In this case, if untreated or even only topically treated, may worsen
with upper respiratory infection, in severe cases with afebrile pneumonitis usually
presenting at 2 to 20 months of age (Darville, 2005). Approximately 50% of infants with
chlamydial pneumonitis have concurrent conjunctivitis or a recent history of conjunctivitis
(Tarabishy et al., 2008).

Fig. 1. Neonatal conjuctivitis due to chlamydia trachomatis in a five days old infant
Staphylococcus conjunctivitis. Staphylococcus aureus can cause neonatal conjuctivitis with
redness, swollen purulent discharge (Figure 2).

Fig. 2. Neonatal conjuctivitis due to staphylococcus aureus infection in an one week old
infant.

3.3 Herpetic conjunctivitis


It is present usually the first two weeks of life with moderate injection, edema of conjuctiva
and nonpurrulent discharge after vesicular skin lesions which can precede the eye
involvment. In some cases it may be complicated with corneal clouding with dentritic or
geographic corneal ulcers or upper respiratory infection (Rudolph, 2002). Systemic infection
can cause jaundice, hepatosplenomegaly, pneumonitis, meningoencephalitis and
disseminated intravascular coagulation.

www.intechopen.com
Ophtalmia Neonatorum 153

Etiology Onset after birth Clinical findings

Mild injection, watery


Chemical 3-36 hours
dicharge

Injection and lead edema,


Gonnococal 1-7 days
purulent discharge

Mild- severe injection, watery-


purulent discharge,
Chlamydial 5-14 days
psudomembranes, chronicity,
associated pneumonia
Watery discharge, injection
Herpetic 1-14 days and lead edema, associated
keratitis

Table 3. Clinical findings of neonatal conjunctivitis by etiological factor modified from


Rudolphs fundametntals of Pediatrics, 2002

4. Diagnosis
Prompt diagnosis is key in establishing proper treatment and minimizing potential serious
complications of disease. An accurate diagnosis of conjunctivitis centers on taking a patient
history to learn when symptoms began, how long the condition has been going on, the
symptoms experienced, and other predisposing factors, such as upper respiratory
complaints, allergies, sexually transmitted diseases, herpes simplex infections, and exposure
to persons with pink eye. It may be helpful to learn whether an aspect of an individual's
occupation may be the cause.
A thorough examination of the globe and periocular structures of a neonate suspected to
have neonatal conjunctivitis is crucial. Corneal involvement should be investigated closely
with and without fluorescein and blue cobalt light. Non-specific signs of neonatal
conjunctivitis include conjunctival injection, tearing, mucopurulent or non-purulent
discharge, chemosis, and eyelid swelling.
Diagnostic tests are usually not indicated unless initial treatment fails or an infection with
gonorrhea or chlamydia is suspected. In such cases, the discharge may be cultured and
stained to determine the organism responsible for causing the condition. Cultures and
smears are relatively painless (Jackson, 2008).
Laboratory studies for suspected infectious etiology should include the following (Table 4
and 5):
Conjunctival scraping, stains for Chlamydia. C. trachomatis is an obligate intracellular
organism and exudates are not adequate for testing so conjunctival specimens for

chlamydia testing must include conjunctival epithelial cells;


Culture on chocolate agar for N gonorrhoeae ;

www.intechopen.com
154 Conjunctivitis A Complex and Multifaceted Disorder

Culture on blood agar for other strains of bacteria;

Culture for HSV if vesicles present or is supicious of viral etiology;


Direct antibody testing or Polymerase Chain Reaction (PCR) may also be indicated.
The laboratory studies may need to be repeated if symptoms worsen or recur following
treatment.

Etiology Laboratory diagnosis

Chemical -

Gonnococal Stain and cultures


Stain, cultures, enzyme immunoassay, direct fluorescent
Chlamydial
antibody assay
Herpetic Stain, cultures, antigen or DNA assay

Table 4. Laboratory diagnosis based on etiology


Modified from Rudolphs fundametntals of Pediatrics, 2002

Etiology Conjuctival Scraping


Minimal reactive cells to few
Chemical
polymorphonuclears
Many reactive cells with gram
Gonococcal
negative intracellular dyplococci
Many reactive cells with stain for
basophilic cytoplasmic inclusion
Chlamydial
bodies or direct immunofluorescent
assay
Other bacteria (Staphylococcus,
Stain for bacteria
Streptococcus, Haemophilus)
Variable reactive cells with
Herpes simplex virus
multinucleated giant cells

Table 5. Conjuctival scraping findings in ophtalmia neonatorum


Modified from Duane's Clinical Ophthalmology, 2008

5. Differential diagnosis

The differential diagnosis of neonatal conjunctivitis includes:

Cellulitis (Orbital, Preseptal)

Dacryocystitis

Glaucoma, Primary or Secondary Congenital


Keratitis, Bacterial, Fungal or Herpes Simplex

www.intechopen.com
Ophtalmia Neonatorum 155

6. Complications
Complications usually can be divided concerning eye and/or systemic complications.
Ocular complications of neonatal conjunctivitis include pseudomembrane formation,
corneal edema, thickened palpebral conjunctivia, peripheral pannus formation, corneal
opacification, staphyloma, corneal perforation, endophthalmitis, loss of eye, and blindness.
Systemic complication due to Chlamydia infection
Systemic complications of chlamydia conjunctivitis include pneumonitis, otitis, pharyngeal
and rectal colonization. Pneumonia has been reported in 10-20% of infants with chlamydial
conjunctivitis.
Systemic complications due to gonococcal infection
Complications of gonococcal conjunctivitis and subsquent systemic involvement include
arthritis, meningitis, anorectal infection, septicemia, and death.
The complications can be avoided if the proper treatment is initiated at time.

7. Treatment
7.1 Initial therapy
Ophtalmia neonatorum is treated with a broad-spectrum antibiotic e.g. ofloxacin 0.3% qds.
When the microbiological results is present the treatment is based on microbiological cause
(Jackason, 2008).

7.2 Chemical ophtalmia neonatorum


Chemical neonatal conjunctivitis usually disappears spontaneously within 2-4 days, and no
treatment is required. The use of artificial tear is preferred.

7.3 Chlamydial ophtalmia neonatorum


The recommended regimen for chlamydial neonatal conjunctivitis is erythromycin base or
ethylsuccinate, as a systemic therapy, 50mg per kg per day orally, divided into four doses
per day for two weeks (Table 6). A follow-up of infants is recommended to determine
whether initial treatment was effective because the efficacy is only approximately 80% and a
second course of therapy might be required. Also, the evaluation of concomitant chlamydial
pneumonia should be considered (Sexually transmitted disease treatment guidelines, 2010;
Lippincott Williams & Wilkins, 2008; Yanoff & Duker, 2008).
The systemic treatment is administred as additional to topical treatment. (Sexually
transmitted disease treatment guidelines, 2010). From local antibiotics usually are applied
erythromycin 0.5% or tetracycline 1% eye ointment.
The mother and her sexual partners also should be treated with erythromycin base or
ethylsuccinate (Sexually transmitted disease treatment guidelines, 2010).

7.4 Gonococcal ophtalmia neonatorum


The immediate treatment is needed because of complications such as corneal perforation
and blindness. Gonococcus conjunctivitis is treated with ceftriaxone 25-50mg/kg IV or IM in
a single dose (Table 6), not to exceed 125mg. An alternative regimen is cefotaxime
100mg/kg/24 hours IV or IM divided in two doses for seven days or 100mg/kg as a single
dose. The irrigation with saline is preferred until the purulent discharge is cleared. The local

www.intechopen.com
156 Conjunctivitis A Complex and Multifaceted Disorder

antibiotics such as bacitracin or erythromycin eye ointment are applied as additional


therapy because topical antibiotic alone is inadequate. The atropine sulphate ointment
should be applied if the cornea is involved (Sexually transmitted disease treatment
guidelines, 2010; Lippincott Williams & Wilkins, 2008; Yanoff & Duker, 2008).
The mothers of infants and mothers sex partners should be evaluated and treated according
to the recommendations for treating gonococcus infections in adults (Sexually transmitted
disease treatment guidelines, 2010).
Neonatal conjunctivitis due to other bacteria usually respond to topical ointments
containing bacitracin for gram positive stain bacteria, and tobramycin or ciprofloxacin for
gram negative stain bacteria.

Type of bacteria Drug Dose for day Duration


Chlamydia
Erythromycin 50mg/kg 14 days
trachomatis
Nesseria gonorrhoeae Ceftriaxone 25-50mg/kg A single dose

Table 6. Recommended regimens for bacterial neonatal conjuctivitis


Modified from Sexually transmitted disease treatment guidelines 2010. Centers for Disease
Control and Prevention, MMWR Recomm Rep 2010; 59 (RR-12): 53-54.

7.5 Herpetic ophtalmia neonatorum


Herpetic neonatal conjunctivitis is recommended to be treated with acyclovir 45-
60mg/kg/day in three doses for 14 days in non disseminated disease and 21 days in
disseminated disease. Local antiviral therapy is 1% trifluridine or 3% vidarabine or 0.1%
iododeoxyuridine (drops or ointment) (Lippincott Williams & Wilkins, 2008).

8. Prophylaxis
8.1 Silver nitrate prophylaxis
German obstetrician Cred', in 1881, has applied 2% silver nitrate solution for prophylaxis of
neonatal ophtalmia, resulting in a reduction of incidence from 7.8% to 0.17%. Thereafter was
started instillation of silver nitrate, based on legislation, in most European countries and
most of North America states in the first half of last century (Schneider, 1984; Crede CSR,
1881; Barasam, 1966). Latest in 1970s approximately half the United States specified 1%
silver nitrate solution as the sole agent (Hammerschlag MR et al., 1908). In the United
Kingdom the procedure has been discontinued, and in Japan and Australia, it was never
used (Shaw EB, 1977). The mother usually can be representative consent of using of Cred's
method in Sweden (Wahlberg V, 1982). The decision for changing of the Wisconsin law in
1980 that tetracycline and erythromycin could be used for prophylaxis against GON was
based on a previous ruling by US Supreme Court (Whittaker N et al., 1981).
The siver nitrate, which by law is instilled within 1 hour after birth, may cause chemical
conjunctivitis pain and visual impairment. The silver nitrate does not prevent all cases of
gonococcal neonatal conjunctivitis. The chemical conjunctivitis caused by silver nitrate may
mask the onset of gonococcus neonatal conjunctivitis (Shaw, 1977; Snowe et al., 1973).

www.intechopen.com
Ophtalmia Neonatorum 157

Since 1940s, when antibiotics were developed the incidence of gonococcal neonatal
conjunctivitis was decreased dramatically (Butterfield et al., 1981).
Recommendations of the US Centers for Disease Control (CDC) are supported from
American Academy of Pediatrics in 1986 and 1988. According to these recommendations 1%
tetracycline ointment and 0.5% erythromycin ointment were equally acceptable in
preventing of gonococcus ophtalmia neonatorum. Although it was felt that silver nitrate
might be the best agent in areas where the incidence of penicillinase-producing neisseria
gonorrhoeae (PPNG) was appreciable (Peter, 1988).
The CDC's 1989 guidelines on the treatment of sexually transmitted diseases were
unchanged with respect to the prevention of ophthalmia neonatorum (Sexually Transmitted
Diseases Treatment Guidelines, 1989).
In Canada the incidence of PPNG among reported cases of gonorrhea increased from 0.5%
in 1985 to 5.5% in 1989 (Status of penicillinase-producing Neisseria gonorrhoeae in
Canada, 1991).
In 1989 the US Preventive Services Task Force recommended that 1% tetracycline ointment or
0.5% erythromycin ointment have to be applied topically to the eyes of all newborns as soon as
possible after birth and no later than 1 hour after birth (Preventive Services task Forces, 1989).
Silver nitrate was not recommended since it is locally irritating, frequently causing chemical
conjunctivitis, and has limited efficacy in preventing chlamydial ophthalmia neonatorum.

8.2 Povidon-iodine prophylaxis


In 1995, is reported the use of a 2.5% povidone-iodine solution for prophylaxis of ophtalmia
neonatorum in Kenya, and was found to be more effective than treatment with
erythromycin or silver nitrate for prophylactic purposes. Also, the povidone-iodine was less
toxic and it costs less (Isenberg et al., 1995).
The povidone-iodine prophylaxis against ophtalmia neonatorum, applied twice in the first
postnatal day over a single application at birth, revealed with no advantage. It was
supported the original notion of Crede in 1881 that a single drop of an effective medication
given at birth is the best way to prevent the development of ophtalmia neonatorum. The
povidone-iodine applications approximately 24 hours later were with no further benefit.

8.3 Antibiotics prophylaxis


The procedure for prevence of gonococcal ophthalmia neonatorum is required by law in
most states. Prophylactic agent should be instilled into the eyes of newborns. But, the
efficacy of prophylactic agents in preventing chlamydial ophthalmia is clearless, and they
do not eliminate nasopharyngeal colonization by C. trachomatis.
This preparation should be instilled into both eyes of every neonate as soon as possible after
delivery. Ideally, ointment should be applied using single-use tubes or ampoules rather than
multiple-use tubes. If prophylaxis is delayed (i.e., not administered in the delivery room), a
monitoring system should be established to ensure that all infants receive prophylaxis. All
infants should be administered ocular prophylaxis, regardless of whether they are delivered
vaginally or by cesarean section.
Antibiotics that are applied in prevention of gonococcal ophtalmia are tetracycline and
erythromycin and are more effective than silver nitrate (Rothenberg, 1979; American Academy
of Pediatrics, 1980). Erythromycin is less effective than tetracycline against sensitive isolates of
N. gonorrhoeae in vitro. Canadian Paediatric Society in 2010 has revised recommandations for
the prevention of neonatal ophthalmia due to N gonorrhoeae (Table 7).

www.intechopen.com
158 Conjunctivitis A Complex and Multifaceted Disorder

Recommendation Category Grade


Prophylaxis to prevent neonatal ophthalmia due to N gonorrhoeae
A 1
should be provided to all infants.
Physicians and their patients may choose among the recommended
prophylactic agents - that is, 1% silver nitrate solution in single-
A 1
dose ampoules, or an ointment containing 0.5% erythromycin base
or 1% tetracycline hydrochloride in single-dose tubes.
The use of povidone-iodine for ophthalmia prophylaxis. C 1
To prevent potential cross-contamination, a separate ampoule or
tube should be used for each eye. Ampoules and tubes should be A 3
discarded after use.
When 1% silver nitrate solution is used, each eyelid should first be
wiped gently with a sterile cotton ball to remove foreign matter and
permit adequate eversion of the lower lid. Two drops of solution are
placed in each lower conjunctival sac. The closed eyelids can be A 3
massaged gently to help spread the solution to all areas of the
conjunctiva. After 1 min, any excess silver nitrate should be gently
wiped from the eyelids and surrounding skin with sterile cotton.
When an ophthalmic ointment (tetracycline or erythromycin) is used,
the eyelids should be prepared as for the application of silver nitrate.
A line of ointment 1 to 2 cm long is placed in each lower conjunctival
sac, if possible covering the whole lower conjunctival area. Care is
A 3
needed to prevent injury to the eye or the eyelid from the tip of the
tube. The closed eyelids can be massaged gently to help spread the
ointment. After 1 min, any excess ointment should be wiped gently
from the eyelids and surrounding skin with a sterile cotton.
The eyes should not be irrigated after instillation of a prophylactic
agent. Irrigation may reduce the efficacy of the agent and probably
A 3
does not decrease the incidence of chemical conjunctivitis caused
by silver nitrate.
Prophylaxis should be given as soon as possible after birth.
However, delaying prophylaxis for up to 1 h after birth probably B 3
does not impair the agent's efficacy.
A check system should be established to ensure that all infants are
A 3
treated.
Infants born by caesarian section should also receive prophylaxis. B 3
Pregnant women should be screened for infection by N
gonorrheoae and C trachomatis during pregnancy and their A 3
identified infections should be treated during pregnancy.
Infants born to women with gonococcal infection discovered
during labour or at the time of delivery should be given a single
A 2
dose of ceftriaxone (25 to 50 mg/kg) or cefotaxime (100 mg/kg) in
addition to topical prophylaxis.

Table 7. Recommandations for the prevention of neonatal ophthalmia due to N gonorrhoeae

www.intechopen.com
Ophtalmia Neonatorum 159

Modified from Canadian Pediatric Society. Revised Recommandations for the prevention of
neonatal ophtalmia, 2010.
Classification used to determine the strength of the recommendations and the quality of the
evidence on which the recommendations are based.

Category Definition
A Good evidence to support a recommendation for use
B Moderate evidence to support a recommendation for use
C Insufficient evidence to support a recommendation for or against use
D Moderate evidence to support a recommendation against use
E Good evidence to support a recommendation against use

Grade
1 Evidence from at least one properly randomized, controlled trial
Evidence from at least one well-designed clinical trial without
randomization, from cohort or case- controlled analytic studies, preferably
2
from more than one centre, from multiple time series, or from dramatic
results in uncontrolled experiments
Evidence from opinions or respected authorities on the basis of clinical
3
experience, descriptive studies or reports of expert committees
Source. Canadian Pediatric Society. Revised Recommandations for the prevention of neonatal
ophtalmia, 2010.
Table 8.
Tetracycline as silver nitrate does not prevent completely chlamydial ophtalmia neonatorum
(Laga et al., 1988, Canadian Task Force on the Periodic Health Examination, 1992). There
were no significant differences between the rates of chlamydial ophtalmia neonatorum
when prophylaxis with erythromycin was compared with prophylaxis with tetracycline or
silver nitrate. For a modest reduction in chlamydial ophtalmia neonatorum now are
recommended the agents for gonococcal prophylaxis.
Erythromycin 0.5 % is the only antibiotic ointment recommended for use in neonates in each
eye in a single application. Silver nitrate and tetracycline ophthalmic ointment are no longer
manufactured in the United States, bacitracin is not effective, while povidone iodine has not
been studied adequately (Sexually Transmitted Diseases Treatment Guidelines, 2010).
If erythromycin ointment is not available, infants at risk for exposure to N. gonorrhoeae
(especially those born to a mother with untreated gonococcus infection or who has received
no prenatal care) can be administered ceftriaxone 25-50 mg/kg IV or IM, not to exceed 125
mg in a single dose (Sexually Transmitted Diseases Treatment Guidelines, 2010).
The diagnosis and treatment of gonococcal and chlamydial infections in pregnant women
is the best method for preventing neonatal gonococcal and chlamydial disease. Also
preventative measures include proper hand-washing techniques by peripartum and
nursery staff.

www.intechopen.com
160 Conjunctivitis A Complex and Multifaceted Disorder

9. Prognosis

Chlamydial infection: good - 80% fully recover after one course of treatment.

Bacterial infection: rarely fails to respond to appropriate treatment.

Viral infection: the ocular prognosis can be poor and the systemic sequelae may be fatal.
Chemical irritation: good - full spontaneous recovery expected after 24-36 hours.

10. References
[1] World Bank. (1993) World development report: investing in health. Oxford. Oxford
University Press.
[2] Sloan NL, Winikoff B, Haberland N, Coggins C, Elias C. (2000) Screening and syndromic
approach to identify gonorrhhoea and chlamydial infection among women. Studies
in Family Planning 31: 55-68.
[3] Lush L, Walt G, Ogden J. (2003) Transferring policies for treating sexually transmitted
infections: whats wrong with global guidelines? Health Policy and planning 18(1):
18-30.
[4] Beers MH, Porter RS, Jones TV, Kaplan JL, Berkwits M. (2006) The Merck Manual of
Diagnosis and Therapy. Merck Research Laboratories.
[5] Rudolph AM, Kamei RK, Overby KJ. (2002) Rudolphs Fundamentals of Pediatrics.
McGraw-Hill.
[6] Hay WW, Levin MJ, Sondheimer JM, Deterding RR. (2009) Current Diagnosis &
Treatment pediatrics. Lange.
[7] Mohile M, Deorari A, Satpathy G, Sharma A, Singh M.(2002) Microbiological study of
neonatal conjunctivitis with special reference to Chlamydia trachomatis. Indian J
Ophtalmol 50:295-99.
[8] Miller K. (2006) Diagnosis and treatment of Chlamydia trachomatis infection. Am Fam
Physician 73:1411-6.
[9] Jatla et al. (2009) Conjuctivitis, Neonatal, Medscape.
[10] Kroner, T. (1884) ZurAetiologie der Opthalmoblennorrhoea Neonatorum.
Zentrablattfiir Gyndkologie 8, 643-645.
[11] Lindner, K. (1909) Uebertragungsversuche von gonokokkenfreier Blennorrhoea
neonatorum auf Affen. WienerKlinische Wochenschrift 22, 1554; 1659-1660.
[12] T'ang, F. F., Chang, H. L., Huang, Y. T., and Wang, K. C. (1957) Studies on the aetiology
of trachoma with special reference to isolation of the virus in chick embryo.
ChineseMedical Journal 75, 429-447.
[13] Jones, B. R., Collier, L. W., and Smith, C. H. (1959) Isolation of virus from inclusion
blennorrhoea. Lancet 1, 902-905.
[14] Rodriguez P, B de Barbeyac K, Persson K, Dutilh B, Bebear C. (1993) Evaluation of
molecular typing for epidemiological study of Chlamydia trachomatis genital
infections. J Clin Microbiol 31:2238-2240.
[15] Luca Gallo Vaulet1, Carolina Entrocassi, Ana I Corominas, Marcelo Rodrguez
Fermepin. (2010) Distribution study of Chlamydia trachomatis genotypes in
symptomatic patients in Buenos Aires, Argentina: association between genotype E
and neonatal conjunctivitisBMC Research Notes 3:34.

www.intechopen.com
Ophtalmia Neonatorum 161

[16] World Health Organisation. (2001) Global prevalence and incidence of selected curable
Sexually Transmitted Infections: overview and estimates. Geneva: WHO.
[17] Schachter J, Grossman M, Sweet RL, Holt J, Jordan C, Bishop E. (1986) Prospective
study of perinatal transmission of Chlamydia trachomatis. JAMA 55:3374-3377.
[18] Numazaki K, Asanuma H, Niida Y. (2003) Chlamydia trachomatis infection in early
neonatal period. BMC Infect Dis 4;3(1):2.
[19] Rosenman MB, Mahon BE, Downs SM, Kleiman MB. (2003) Oral erythromycin
prophylaxis vs watchful waiting in caring for newborns exposed to Chlamydia
trachomatis. Arch Pediatr Adolesc Med 157(6):565-71.
[20] Hobson D. (1977) Chlamydial infection in neonates. New Eng J Med 1977:296:398.
[21] Valencia C, Prado V, Rios M, Cruz MA, Pilorget JJ. (2000) Prevalence of the Chlamydia
trachomatis in neonatal conjunctivitis determination by indirect fluorescente and
gene amplification. Rev Med Chil. 128(7):758-65. 8.
[22] Olatunji FO. (2004) A case control study of ophthalmia neonatorum in Kaduna II:
causative agents and their antibiotic sensitivity. West Afr J Med. 23(3):215-20.
[23] Kampmeier RH. (1978) Identification of the gonococcus by Albert Neisser. Sex Transm
Dis 5:71-72.
[24] Morton RS (ed). (1977) Gonorrhoea [Vol. 9 in the series Major Problems in
Dermatology]. Philadelphia, W.B. Saunders.
[25] Di Bartolomeo S, Mirta DH, Janer M, et al. (2001) Incidence of Chlamydia trachomatis
and other potential pathogens in neonatal conjunctivitis. Int J Infect Dis 5(3);139-
43.
[26] Noegel A, Gotschlich EC. (1983) Isolation of a high molecular weight polyphosphate
from Neisseria gonorrhoeae. J Exp Med 157:2049-2060.
[27] Naumann M, Wessler S, Bartsch C, et al. (1997) Neisseria gonorrhoeae epithelial cell
interaction leads to the activation of the transcription factors nuclear factor kappaB
and activator protein 1 and the induction of inflammatory cytokines. J Exp Med
186:247-258.
[28] Ramsey KH, Schneide H, Cross AS, et al. (1995) Inflammatory cytokines produced in
response to experimental human gonorrhea. J Infect Dis 172:186-191.
[29] Alexey JM, So M. (2000) Interactions of pathogenic Neisseriae with epithelial cell
membranes. Ann Rev Cell Dev Biol 16:423-57.
[30] Naumann M, Rudel T, Meyer TF. (1999) Host cell interactions and signaling with
Neisseria gonorrhoeae. Curr Opin Microbiol 2:62-70.
[31] Gregg CR, Melly MA, Hellerqvist CG, et al. (1983) Toxic activity of purified
lipopolysaccharide as N. gonorrhoeae for human fallopian tube mucosa. J Infect Dis
143:432-439.
[32] Casey SG, Shafer WM, Spitznagel JK. (1986) Neisseria gonorrhoeae survive
intraleukocytic oxygen-independent antimicrobial capacities of anaerobic and
aerobic granulocytes in the presence of pyocin lethal for extracellular gonococci.
Infect Immun 52:384-389.
[33] Shafer WM, Onunka VC, Martin LE. (1986) Antigonococcal activity of human
neutrophil cathepsin G. Infect Immun 54:184-188.

www.intechopen.com
162 Conjunctivitis A Complex and Multifaceted Disorder

[34] Kallstrom H, Liszewski MK, Atkinson JP, et al. (1997) Membrane cofactor protein (MCP
or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol Microbiol 25:639-
647.
[35] Gutman LT. (2001) Gonococcal infections, in Remington JS, Klein JO (eds): Infectious
Diseases of the Fetus and Newborn Infant (ed 5). Philadelphia, W.B. Saunders Co.,
pp 1199-1215.
[36] Friendly DS. (1969) Gonococcal conjunctivitis of the newborn. Clin Prac Child Hosp
25:1-9.
[37] Cimolai N. (2006) Ocular methicillin-resistant Staphylococcus aureus infections in a
newborn intensive care cohort. Am J Ophthalmol 142(1): 183-4.
[38] Hedberg K, Ristinen TL, Soler JT, White KE, Hedberg CW, Osterholm MT, MacDonald
KL.(1990) Outbreak of erythromycin-resistant staphylococcus conjunctivitis in a
newborn nursery. Pediatr Infect Dis J 9(4):268-73.
[39] Pschl JM, Hellstern G, Ruef P, Bauer J, Linderkamp O. (2002) Ophtalmia neonatorum
caused by B Streptococcus. Scand J Infect Dis 34(12):921-2.
[40] Chhabra MS, Motley WW 3rd, Mortensen JE. (2008) Eikenella corrodens as a causative
agent for neonatal conjunctivitis.JAAPOS 12(5): 524-5.
[41] Martinez Ruiz MT, Ascaso Puyuelo FJ, Navales Bertol, Palomar Gmez MT, Garca
Garca C, Olivares Lpez JL. (1993) Neonatal conjunctivitis: microbiologic study
and antibiotic sensitivity. An Esp Pediatr 39(1);42-5.
[42] Olatunji FO, Fadeyi A, Ayanniyi AA, Akanbi AA 2nd. (2007) Non-gonococcal bacterial
agents of conjunctivitis and their antibiotic susceptibility patterns in llorin, Nigeria.
Afr J Med Sci 36(3):243-7.
[43] Overall JC Jr. (1994) Herpes simplex virus infection of the fetus and newborn. Pediatr
Ann 23: 131-136.
[44] Gichuhi S et al. Risk factors for neonatal conjunctivitis in babies of HIV-1 infected
mothers. (2009) Ophthalmic Epidemiol 16(6):337-45.
[45] Wu J et al. (2009) Influence of premature rupture of membranes on neonatal
health. Zhonghua Er Ke Za Zhi 47(6):452-6. 5.
[46] Foster A, Klauss V. (1995) Ophtalmia neonatorum in developing countries. N Engl J
Med 332: 600-601.
[47] Woods, CR. (2005) Gonococcal infections in neonates and young children. Semin
Pediatr Infect Dis 16: 258-270.
[48] Zar HJ. (2005) Neonatal chlamydial infections: prevention and treatment. Paediatr
Drugs : 103-110.
[49] Isenberg SJ, Apt L, Wood M. (1996) The influence of prenatal factors on ophthalmia
neonatorum. J Pediatr Ophthalmol Strabismus 33:185-188.
[50] Chandler JW, Rapoza PA. (1990) Ophtalmia neonatorum. Int Ophthalmol Clin 30: 36-38.
[51] Vaz FA, Ceccon ME, Diniz EM. (1999) Chlamydia trachomatisinfection in the neonatal
period: clinical and laboratory aspects. Experience of a decade: 1987- 1998. Rev
Assoc Med Bras 45: 303-311.
[52] Schachter J, Grossman M, Sweet RL, Holt J, Jordan C, et al. (1986) Prospective study of
perinatal transmission of Chlamydia trachomatis. JAMA 255: 3374-7.

www.intechopen.com
Ophtalmia Neonatorum 163

[53] Hollier LM, Wendel GD. (2009) Third trimester antiviral prophylaxis for preventing
maternal genital herpes simplex (HSV) recurrences and neonatal infection.
Cochrane Database Syst Rev 1:CD004946.
[54] Roberts S. (2009) Herpes simplex virus: incidence of neonatal herpes simplex virus,
maternal screening, management during pregnancy and HIV. Curr Opin Obstet
Gynecol 21: 124-130.
[55] Tarabishy AB, Jeng BH. (2008) Bacterial conjunctivitis: areview for internists. Cleve Clin
J Med 75: 507-512.
[56] Yip PP et al. (2008) The use of polymerase chain reaction assay versus conventional
methods in detecting neonatal chlamydial conjunctivitis. J Pediatr Ophthalmol
Strabismus 45(4):234-9.
[57] Rubenstein JB, Virasch V. (2008) Conjunctivitis: infectious and noninfectious. In: Yanoff
M, Duker JS, eds. Ophthalmology. 3rd ed. Philadelphia, Pa: Mosby Elsevier.
[58] Jackson TL. (2008) Moorfields Manual of Ophtalmology, Mosby.
[59] Ophthalmia neonatorum (Newborn conjunctivitis). (2008) Wills Eye Manual.
Philiadelphia.PA: Lippincott Williams & Wilkins 181-183.
[60] Ophthalmia neonatorum. (2008) Yanoff & Duker: Ophthalmology, 3rd edition. Mosby.
[61] Sexually transmitted disease treatment guidelines 2010. (2010) Centers for Disease
Control and Prevention, MMWR Recomm Rep; 59 (RR-12): 47-48.
[62] Schneider G. (1984) Silver nitrate prophylaxis. Can Med Assoc J 131(3): 193196.
[63] Crede CSR. (1881) Die Verhutung der Augentzundung der Neugeborenen. Arch
Gynakol 18: 367-370.
[64] Barsam PC. (1966) Specific prophylaxis of gonorrheal ophthalmia neonatorum; a
review. N Engl J Med 274: 731-734.
[65] Hammerchlag MR, Chandler JW, Alexander ER et al. (1980) Erythromycin ointment for
ocular prophylaxis of neonatal chlamydial infection. JAMA 244: 2291-2293.
[66] Shaw EB. (1977) Comment on silver nitrate prophylaxis [C]. Pediatrics 60: 773.
[67] Wahlberg V. (1982) Reconsideration of Cred prophylaxis. Introduction. Acta Pediatr
Scand [Suppl] 295: 9-25.
[68] Whittaker N, Strasser J. (1981) The silver nitrate challenge. Mother Mag 27-30.
[69] Snowe RJ, Wilfert CM. (1973) Epidemic reappearance of gonococcal ophthalmia
neonatorum. Pediatrics 51: 110-114.
[70] Butterfield PM, Ende RN, Svejda MJ. (1981) Does the early application of silver nitrate
impair maternal attachment? Pediatrics 67: 737-738.
[71] Peter G (ed). (1988) 1988 Red Boot Report of the Committee on Infectious Diseases, 21st
ed, Am Acad Pediatr, Elk GroveVillage, Ill.
[72] 1989 Sexually Transmitted Diseases Treatment Guidelines. (1989) MMWR 38 (S-8): 27.
[73] Status of penicillinase-producing Neisseria gonorrhoeae in Canada- 1989. (1991) Can
Dis Wkly Rep. 17: 49-50.
[74] US Preventive Services Task Force. (1989) Guide to Clinical Preventive Services,
Williams & Wilkins, Baltimore, 136.
[75] Isenberg SJ, Apt L, Wood M. (1995) A controlled trial of povidone-iodine as prophylaxis
against ophthalmia neonatorum. New Eng J Med 332:5626.
[76] Rothenberg R. (1979) Ophthalmia neonatorum due to Neisseria gonorrhea: prevention
and treatment. Sex Trans Dis 6(Suppl 2):187-91.

www.intechopen.com
164 Conjunctivitis A Complex and Multifaceted Disorder

[77] American Academy of Pediatrics. (1980) Prophylaxis and treatment of neonatal


gonococcal infections. Pediatrics 65:1047-50.
[78] Laga M, Plummer FA, Piot P, et al. (1988) Prophylaxis of gonococcal and chlamydial
ophthalmia neonatorum. A comparison of silver nitrate and tetracycline. N Engl J
Med 318:653-7.
[79] Canadian Task Force on the Periodic Health Examination. (1992) Periodic health
examination, 1992 update: 4. Prophylaxis for gonococcal and chlamydial ophthalmia
neonatorum. CMAJ 147:1449-54. Jatla, 2009; Sexually Transmitted Diseases Treatment
Guidelines.

www.intechopen.com
Conjunctivitis - A Complex and Multifaceted Disorder
Edited by Prof. Zdenek Pelikan

ISBN 978-953-307-750-5
Hard cover, 232 pages
Publisher InTech
Published online 23, November, 2011
Published in print edition November, 2011

This book presents a number of interesting and useful aspects and facets concerning the clinical features,
properties and therapeutical management of this condition. Dr. H. Meja-Lpez et al. present an interesting
survey of the world-wide epidemiologic aspects of infectious conjunctivitis. Dr. U. Ubani evaluates conjunctival
symptoms/signs participating in the clinical features of this disorder. Dr. A. Robles-Contreras et al. discuss
immunologic aspects underlying possibly the conjunctivitis. Dr. Z. Pelikan presents the cytologic and
concentration changes of some mediators and cytokines in the tears accompanying the secondary conjunctival
response induced by the nasal challenge with allergen. Dr. S. Sahoo et al. summarize the treatment and
pharmacologic control of particular clinical forms of conjunctivitis in general practice. Dr. S. Leonardi et al.
explain the basic pharmacologic effects of leukotriene antagonists and their use for the treatment of allergic
conjunctivitis. Dr. J.A. Capriotti et al. evaluate the therapeutical effects of various anti-adenoviral agents on the
acute conjunctivitis caused by adenovirus. Dr. V. Vanzzini-Zago et al. assess the prophylactic use and efficacy
of "povidone-iodium solution", prior the ocular surgery. Dr. F. Abazi et al. present the clinical features,
diagnostic and therapeutical aspects of "neonatal conjunctivitis". Dr. I.A. Chaudhry et al. review the special
sub-form of conjunctivitis, being a part of the "Trachoma". Dr. B. Kwiatkowska and Dr. M. Maliska describe
the clinical, pathophysiologic and immunologic features of conjunctivitis. Dr. S. Naem reviews the conjunctivitis
form caused by Thelazia nematodes, occurring principally in animals.

How to reference
In order to correctly reference this scholarly work, feel free to copy and paste the following:

Flora Abazi, Mirlinda Kubati, Blerim Berisha, Masar Gashi, Dardan Kocinaj and Xhevdet Krasniqi (2011).
Ophtalmia Neonatorum, Conjunctivitis - A Complex and Multifaceted Disorder, Prof. Zdenek Pelikan (Ed.),
ISBN: 978-953-307-750-5, InTech, Available from: http://www.intechopen.com/books/conjunctivitis-a-complex-
and-multifaceted-disorder/ophtalmia-neonatorum

InTech Europe InTech China


University Campus STeP Ri Unit 405, Office Block, Hotel Equatorial Shanghai
Slavka Krautzeka 83/A No.65, Yan An Road (West), Shanghai, 200040, China
51000 Rijeka, Croatia
Phone: +385 (51) 770 447 Phone: +86-21-62489820
Fax: +86-21-62489821

www.intechopen.com
Fax: +385 (51) 686 166 Fax: +86-21-62489821
www.intechopen.com

Você também pode gostar